The goals of this career development award are to provide training to Bradley Dougherty, OD, MS in patient-oriented research and to determine the relationships among stress and depression, C-reactive protein, the complement factor Y402H polymorphism, and age-related macular degeneration (AMD) treatment outcomes. The proposal includes a five-year career development plan consisting of formal coursework, training in laboratory techniques and psychoneuroimmunology, and interaction with mentors. The proposal addresses several NEI objectives including to explore the pathophysiological heterogeneity of AMD to hasten development of the tools needed for improved diagnosis, prevention, and therapy and to encourage the multidisciplinary collaboration and training of researchers from other areas about issues pertinent to visual impairment. Findings from the field of psychoneuroimmunology have clearly demonstrated that stress and depression are related to increased levels of systemic inflammatory markers, including C-reactive protein (CRP), and other immune system dysfunction. Inflammation plays a key role in the pathology of AMD. Higher levels of CRP and the presence of the Y402H polymorphism are related to prevalence and progression of AMD. Patients are particularly likely to experience stress and depression in the period immediately following new vision loss from neovascular AMD. Recent advances in treatment for AMD, specifically anti-VEGF injections, have shown promise in restoring vision, yet evidence remains that stress and depression are still marked in patients undergoing these treatments. The aims of the proposed research project are to test whether stress and depression in patients undergoing treatment for AMD are related to poorer treatment outcomes, whether this effect is mediated by CRP, and whether higher CRP and the Y402H polymorphism are related to poorer treatment outcomes. One hundred sixty patients with neovascular AMD will be enrolled in the study. The primary outcome measure is change in visual acuity from baseline to 12 months. A secondary outcome measure will be change in patient-reported visual function.